Differentiation of human epidermis-derived mesenchymal stem cell-like pluripotent cells into neural-like cells in culture and after transplantation

Skin is the largest organ of the human body and a possible source of stem cells for research and cell-based therapy. We have isolated a population of mesenchymal stem cell-like pluripotent cells from human epidermis, termed human (h) EMSCPCs. This preliminary study tested if these hEMSCPCs can be induced to differentiate into neural-like cells. Human EMSCPCs were first cultured for four to seven days in a serum-free neural stem cell (NSC) medium for pre-induction. During pre-induction, hEMSCPCs coalesced into dense spheres that resembled neural rosettes. In the presence of a conditioned differentiation medium, pre-induced cells took on the morphological characteristics of neural cells, including slender projections with inflated or claw-like ends that contacted the soma or projections of other cells as revealed by confocal microscopy. Moreover, these differentiating cells expressed the neural-specific markers β-III tubulin, MAP2, GFAP, and synapsin I as evidenced by immunocytochemistry. Both pre-induced hEMSCPCs and uninduced hEMSCPCs were labeled with CM-DiI and transplanted into the vitreous cavities of nude mice. Transplanted cells were examined four weeks later in frozen eyeball sections by immunofluorescence staining, which demonstrated superior retinal migration and neural differentiation of pre-induced cells. Our study is the first to demonstrate that hEMSCPCs possess the capacity to differentiate into neural-like cells, suggesting potential uses for the treatment of retinal diseases such as age-related macular degeneration.